USE OF PRECISION-CUT LIVER SLICES FOR STUDIES OF UNSCHEDULED DNA-SYNTHESIS

Precision-cut liver slices were prepared from untreated and Aroclor 12 54 (ARO)-treated male Sprague Dawley rats with a Krumdieck tissue slic er. Liver slices were cultured For 24 hr in medium containing [H-3]thy midine and 0-0.1 mM 2-acetylaminofluorene (2-AAF) using a dynamic orga n culture system and processed for autoradiographic evaluation of unsc heduled DNA synthesis (UDS). Compared with control (i.e. 0 mM 2-AAF) l iver slice cultures, 2-AAF produced a concentration-dependent increase in UDS, the effect being more marked in liver slices from ARO-treated than from untreated rats. With liver slices from untreated rats, 2-AA F produced the greatest increase in UDS in centrilobular hepatocytes. 2-AAF-induced UDS in liver slices from ARO-treated rats was most marke d in centrilobular hepatocytes but the effect also extended to other a reas of the liver lobule. These results demonstrate that precision-cut liver slices may be a valuable alternative in vitro system to hepatoc yte cultures for screening chemicals for potential genotoxicity. Unlik e hepatocyte cultures, liver slices permit the study of zonal differen ces in UDS. Moreover, this technique could be applied to other tissues and the study of species differences in response.